One of the most common diseases in newly received stocker and feedlot cattle is the Bovine Respiratory Disease (BRD) complex. BRD accounts for approximately 75% of morbidity and over 50% of mortality in feedlots (Edwards, A. 1996. Bovine Pract. 30:5). Studies have indicated that BRD manifests its economic losses cumulatively—through the cost of treatment, the cost of lost production and/or salvage, and the cost of death loss (Perino, L. J. 1992. Compend. Cont. Educ. Pract. Vet. 14 (Suppl.):3) These losses make BRD one of the most costly diseases affecting feedlot cattle. Respiratory tract lesions at slaughter correlate with feedlot and carcass performance (Gardner, B. A. et al. 1999. J. Anim. Sci. 77:3168).
In a recent study of the affects of BRD, heifers treated during the study period had lower average daily gain during the period. Heifers treated for BRD had lower marbling scores resulting in a 37.9% reduction in the percentage of carcasses grading U.S.D.A. Choice, or above. Heifers never treated produced a net return (carcass basis) that was $11.48/head more than heifers treated once for BRD, and $37.34/head more than those treated two or more times. (Stovall, T. C., et al. Impact of Bovine Respiratory Disease During the Receiving Period on Feedlot Performance and Carcass Traits, Animal Science Research Report. Oklahoma Agricultural Experiment Station, Oklahoma State University, Stillwater, Okla., USA, 2000.)
Other diseases are of equal or greater economic importance to the cattle industry, which has historically sought to protect livestock from disease, both for economic and public confidence reasons. Immunization of cattle as a means of preventing disease is a common and long-standing practice dating back to Jenner and Pasteur. Immunization is the practice wherein pathogenic biological agents (viruses, bacteria, fungus, rickettsia, protozoa, mycoplasma) have been inactivated, attenuated administered with or without immuno-modulating agents (adjuvants) to animals with the intent of stimulating the animal's immune system such that subsequent exposure to the immunizing or natural agent yields a rapid and specific protective response, thereby avoiding or reducing the severity of disease.
The common means by which commercial vaccines have been administered to animals involves injecting (by use of hypodermic needles) the vaccine material in the skin (intradermal “ID”), in the muscle (intramuscular “IM”), in the subcutaneous tissue (“SC” or “sub-Q”)) or applying the product to readily available mucus membranes (in the eye (intraocular “IO”), in the oral cavity (peros “PO”), or in the nasal cavity (intranasal “IN”)). Although the poultry industry has used aerosols and water as means of vaccine delivery to large numbers of birds, and the swine industry has used water as a delivery method, there are no aerosol, water or feed vaccines approved for commercial use in cattle, dogs, cats or horses.
In the case of injected products (pharmaceutical or biological), a number of concerns arise. With respect to food safety and consumer concern about meat quality, introduction of material into the animal via injection carries with it the potential of altering the edible product by scaring, staining, infection or adulteration due to components of the product and/or by carrying foreign material into the body as a result of the injection process as well as the potential for needles being left in the animal. The National Cattlemen's Beef Association has identified losses associated with injection site reactions resulting in damage to the animal, meat, hides and undermining consumer confidence in the safety and quality of beef. Additionally, injection requires close physical contact between the animal and the person administering the vaccine. This close physical contact entails risk of injury to both the animal and the person. There is a potential for accidental injection of workers or non-target animals. Proper disposal of used needles is an ongoing concern. With respect to application of the vaccine, it is difficult to assure or identify proper deposition of the dose volume into the approved target tissue, particularly under modern management practices where large numbers of animals are rapidly processed. Injection of companion animals (dog, cat, horse) has animal welfare and owner acceptability concerns as well as the potential for infection, pain and tissue damage at the site of administration,
Administration via mucus membranes has several advantages over injected vaccines. Entry of foreign material into edible tissues is avoided. Some pharmaceutical products (insulin—West Pharmaceuticals) have been shown to perform better when applied to mucus membranes as compared to IM or SC injection. The natural route of exposure to the common respiratory and enteric pathogens is via the oral and or nasal route. Stimulation of a mucosally active immune response is better able to prevent or minimize colonization (a prerequisite to infection and disease) by invading pathogens.
Additionally, intranasal administration of vaccines typically stimulates a rapid response and has been shown to be effective in the presence of maternal antibody. There are, however, drawbacks to commercially available cattle vaccines. Products approved for intranasal administration require direct deposition of the vaccine into the nasal cavity (one or both naries). This is stressful to the animal and requires restraint and close physical contact between the animal and person administering the vaccine. In addition, the animal's immediate response is to resist head restraint and attempt to dispel the injected material from the nasal cavity during or immediately following vaccine administration, sometimes into the operator's face, with resulting safety and efficacy concerns.
Water and feed have been used experimentally as a means of vaccine delivery to cattle, however, there are concerns relating to proper dose intake of individual animals. There are no commercial cattle vaccines currently approved for use via feed or water.
Mucosal administration of vaccines has been shown to provide a broad based immune response. This involves both a local and systemic response. Traditionally, vaccines used for mucosal administration have been live or attenuated; as killed antigens tended to be minimally effective when given IN or PO. While live or attenuated vaccines provide a rapid response, the duration of immunity has typically been less than with IM administered products. With the advancement in adjuvant technology and vaccine formulation, it is now possible to increase the duration of immunity as well as allow use of inactivated antigens via the mucosal route. Advancement in formulation of pharmaceutical preparations has also led to development efforts for orally and/or nasally administered products (West Pharmaceutical).
Despite the advances in intranasal and other mucosal administrations of vaccination and therapeutic materials, there remain many needs in the development of safe, effective, and efficient methods of administration of such materials to animals. In particular, the following needs remain unmet by the methods of the prior art:
1. The need to avoid use of needles which may (a) cause damage to edible tissues and hides, (b) incite consumer concern over pet and livestock animal welfare, (c) incite consumer and food industry concern over food safety, (d) raise concerns related to worker safety, and (e) give rise to issues concerning disposal of contaminated medical waste.
2. The need and desire to administer the vaccine to mucosal membranes which is the natural route of infection.
3. The need to avoid (or minimize) close physical contact between the worker and animal in order to reduce the risk of injuries to both.
4. The need to have a visual indicator of vaccination in order to increase compliance and proper administration of vaccine, and to reduce inadvertent multiple vaccination.